The principle aim of this ongoing project is to determine the model of action on single neurons in the mammalian (rat) nervous system of drugs known to produce psychotogenic or hallucinogenic effects in humans. Two main groups of psychotogenic drugs are under study: the "psychedelics" (e.g. LSD and psilocin) and the "amphetamines". An associated goal is to study the basic neurobiology of neuronal systems (e.g. serotonergic, noradrenergic, dopaminergic) upon which the psychotogenic drugs act. The principal methods employed are that of single-cell recording, microiontophoresis, and electrical stimulation of anatomically identified pathways. Work during the current year has included: (1) Continuation of studies on the effects of LSD and other psychotogenic drugs on the firing of neurons in the serotonergic system. (2) Continuation of studies on afferent inputs to serotonergic neurons of the raphe nuclei. (3) initiation of studies on sub- and supersensitivity of serotonergic receptors with respect to serotonin, LSD and other indoleamines. (4) Continuation of studies on catecholaminergic neurons (including effects of amphetamines). In general, the results show that psychotogenic drugs have powerful direct or indirect actions upon monoaminergic neurons; such actions may mediate the behavioral effects of these drugs. BIBLIOGRAPHIC REFERENCES: Gallager, D.W. and Aghajanian, G.K. Inhibition of firing of raphe neurons by tryptophan and 5-hydroxytryptophan: bloackade of inhibiting serotonin synthesis with RO4-4602. Neuropharmacology 15: 149-156, 1976. Bunney, B.S. and Aghajanian, G.K. The precise location of nigral afferents in the rat as determined by a retrograde tracing technique. Brain Research 117: 423-435, 1976.